Millions of Americans use illicit opioids or cocaine, which has substantial individual and public health consequences. Because the opioid and cocaine epidemics intersect with the HIV epidemic, it is crucial to fully understand and mitigate the impact that drug use has on HIV disease. Given that adherence to antiretrovirals (ARVs) is a critical predictor of HIV viral load (VL) suppression, research has focused on the association between illicit drug use and medication non-adherence. It is widely accepted that HIV-infected drug users must engage in drug treatment and strive for abstinence to successfully adhere to ARVs and manage their HIV disease. However, drug use disorders are chronic and relapsing conditions, and many drug users are unable to achieve long-term abstinence. Beyond engagement in drug treatment, little is known about which strategies drug users could use to achieve optimal HIV outcomes. In an ongoing NIH-funded study, we surprisingly found that nearly half of active drug users we screened achieved VL suppression despite ongoing drug use. Therefore, using a mixed methods approach that builds on the resilience of HIV-infected drug users, this study will explore factors and behaviors that facilitate achieving VL suppression among active drug users, regardless of their ability to achieve abstinence. Our exploration will be guided by harm reduction and socioecological models. We will leverage our ongoing NIH-funded study to efficiently recruit and screen participants, and extract their medical record data. We will enroll a total of 170 HIV-infected active drug users, including active illicit opioid users with suppressed VL, active illicit opioid users with non-suppressed VL, active cocaine users with suppressed VL, and active cocaine users with non-suppressed VL. We will also enroll 10 experts in the field of HIV and drug use. The 3 study aims are to: 1) Qualitatively explore HIV- infected active drug users' perceptions of how to achieve optimal HIV health outcomes; 2) Develop a quantitative questionnaire to measure factors and behaviors identified in Aim 1 for analyses proposed in Aim 3; and 3) Quantitatively explore factors and behaviors associated with HIV-infected active drug users achieving optimal HIV health outcomes. This study will improve understanding of drug users' resilience, namely how they are able to achieve optimal HIV outcomes even without abstinence. Findings from this study will ultimately be used to inform the development of an intervention to help HIV-infected active drug users achieve VL suppression.